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PubMed2001

Is pruritus in chronic uremic patients related to peripheral somatic and autonomic neuropathy? Study by R-R interval variation test (RRIV) and by sympathetic skin response (SSR).

The problem of pruritus in uremic dialysed patients remains unsolved. The etiology of pruritus has not been precisely explained, and sometimes no efficient treatment is available. The aim of this study was to analyse the relationship between somatic neuropathy and pruritus as well as the relationship between pruritus and dysautonomia. Fifty-one patients with end-stage renal failure underwent basic neurological examination, nerve conduction velocity studies, and pruritus assessment by means of a questionnaire. Two tests were used to assess the autonomic nervous system, namely the R-R interval variation test in basal and profound breath conditions (RRIV) and the sympathetic skin response (SSR). Pruritus was found in 63% patients of the sample. Most of them had clinical symptoms and signs of peripheral sensorimotor neuropathy and dysautonomia. About 59% of uremic patients revealed abnormally reduced RRIV. About 45% of patients had abnormal (delayed or absent) SSR. The pruritus in uremic patients occurred significantly more frequently (P < 0.01) in patients with paresthesia. A nonsignificant but sizeable trend towards a relationship of pruritus with hypohidrosis and pathological SSR results was also observed. There was no relationship between the pruritus presence and RRIV results. According to our results the activity of the nervous system might play an important role in the mechanism of uremic pruritus, but paradoxically this latter appeared more tightly related to somatic neuropathy than to autonomic dysfunction. Our results also suggest that SSR may become a useful technique for the assessment of autonomic dysfunction in uremic patients.

Adolescent↗
PubMed1996

Autonomic neuropathy in hemodialysis patients treated with recombinant human erythropoietin.

Autonomic nervous system (ANS) function was evaluated in hemodialysis patients treated with recombinant human erythropoietin (rHu-EPO) before and after therapy, in an effort to evaluate the role of anemia in the genesis of autonomic dysfunction in chronic renal failure (CRF). Studies were conducted using a battery of five cardiovascular reflex tests: Valsalva maneuver, handgrip exercise, heart rate response to standing (30:15 index), post-Valsalva rise in blood pressure and postural drop in blood pressure. The patients were divided into two groups: group I consisted of 14 patients on maintenance hemodialysis treated with rHu-EPO for one year, and group II-13 hemodialysis patients treated with rHu-EPO for two years. The results of the tests were compared before and after the correction of anemia by rHu-EPO in each group, as well as with the control group of ten healthy subjects. Data show that renal anemia is not implicated in the genesis of ANS dysfunction in hemodialysis patients, since correction of same by rHu-EPO does not improve the autonomic dysfunction.

Adolescent↗
PubMed2004

A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy.

AIMS: Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. METHODS: Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]. CONCLUSION: Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications.

Adolescent↗
PubMed2005

Assessment of the influence of exercise on heart rate variability in anxiety patients.

OBJECTIVES: The aim of the study was to determine the status of the autonomic nervous system (ANS) in anxiety disorder patients and to evaluate possible exercise intervention in order to improve the ANS and overall psychiatric status of patients. PATIENTS AND METHODS: The ANS function was monitored via means of heart rate variability (HRV) changes during a 6-week hospitalization at the Psychiatric Clinic of University Hospital in Olomouc. The status of ANS was monitored by the new evaluation method of spectral analysis (SA) of HRV. The research involved 43 anxiety patients (29 women and 14 men) who underwent six weeks of intensive psychotherapy; part of the test group also participated in regular aerobic exercise. RESULTS: In the sense of autonomic dysfunction we can not give clear-cut answers to the question whether the autonomic dysfunction could be one of the predictors of anxiety disorder, although our results suggest lower vagal representation in the spectra. Unlike in the healthy population the exercise had a positive impact only on a limited number of patients. Regular endurance exercise on a stationary bicycle had a positive impact on the ANS efficiency only in patients with primary ANS activity reduction. In patients with normal ANS efficiency the exercise intervention had no effect; in some cases we even found activity reduction during the hospitalization period. However, the exercise had a positive effect on the course and outcome of the applied therapy in all patients. CONCLUSIONS: ANS disturbances have not been exhibited in some patients suffering from anxiety disorder. Due to the positive impact of regular physical activity on cardiovascular, metabolic, neural, and psychological changes in organism, monitored exercise should be implemented into therapeutic programs for patients with anxiety disorders.

Adult↗
PubMed1984

Speech symptoms associated with early signs of Shy Drager syndrome.

Speech disturbances reflecting impaired laryngeal control were found in ten patients whose autonomic dysfunction was associated with central neurological disease (Shy Drager Syndrome). In contrast, ten patients with progressive autonomic failure without evidence of CNS involvement had no difficulties on speech function tasks in comparison with normal controls. Presence of speech symptoms may aid in the clinical differentiation between patients with pure autonomic dysfunction and those with central neurological involvement.

Adult↗
PubMed2003

Role of autonomic nervous dysfunction in electrocardio-graphic abnormalities and cardiac injury in patients with acute subarachnoid hemorrhage.

Electrocardiographic abnormalities, cardiac injury, and autonomic nervous function were investigated in patients with acute-phase subarachnoid hemorrhage (SAH) (42 patients with SAH related to ruptured aneurysm and 42 control subjects). Electrocardiogram and Holter electrocardiogram for spectral analysis of heart rate variability (HRV) were recorded. Concentrations of cardiogenic enzymes (ie, creatine kinase-myocardial fraction [CK-MB], myosin light chain I, and troponin T), plasma concentrations of catecholamine (ie, noradrenaline, adrenaline, 3-methoxy-4-hydroxy-phenylethylene glycol [MHPG]) and HRV were compared in the acute and chronic phase of SAH, and with the values in the controls subjects. As previously reported, patients with acute SAH exhibited electrocardiographic (ECG) abnormalities and increased concentrations of both cardiogenic enzymes and plasma catecholamines, suggesting that acceleration of sympathetic activity is involved. However, HRV analysis showed enhanced parasympathetic activity, probably associated with increased intracranial pressure after the onset of SAH, which may be explained by accentuated antagonism, negative feedback of noradrenaline to the center, and reduction of sympathetic activity after reaching a peak level. The results suggest that not only sympathetic activity but also vagal activity is enhanced during the acute phase of SAH, thus contributing to the ECG abnormalities and the onset of cardiac injury.

Acute Disease↗
PubMed2003

Evaluation and treatment of autonomic disorders of the gastrointestinal tract.

Despite the extensive impact of autonomic function on the gastrointestinal system, there is little understanding of the mechanisms by which specific autonomic abnormalities translate into particular gastrointestinal complaints. Three logical alternatives include: (1) the underlying disorder affects the autonomic and gastrointestinal systems independently; (2) autonomic dysfunction alters gastrointestinal processing directly; (3) gastrointestinal manifestations arise as a delayed, indirect consequence of autonomic dysfunction. The major gastrointestinal manifestations of dysautonomia include esophageal dysmotility such as achalasia, gastroparesis, and small bowel bacterial overgrowth in the upper tract. Lower tract disorders include diarrhea, fecal incontinence, and constipation. Sorting through the varied causes of these disorders requires a careful history and examination in each patient. Supportive diagnostic studies may include radionuclide imaging, motility examination, and electrogastrography. Autonomic studies can (1) distinguish a purely enteric from a more generalized dysautonomia; (2) provide surrogate information about motility; (3) differentiate primary (e.g., multiple system atrophy) from secondary (e.g., irritable bowel syndrome) dysautonomias as the etiology of gastrointestinal symptoms. Several new strategies are available for the treatment of gastroparesis, constipation, irritable bowel, and sphincteric incontinence.

Animals↗
PubMed1999

Autonomic function in patients with chronic fatigue syndrome.

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4 +/- 10.5 beats) than in healthy controls (32.2 +/- 9.5) (p = 0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6 +/-8.9 beats) and the control group (40.2 +/- 8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6 +/- 9.9) than in the control group (29.5 +/- 16.7) (p < 0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.

Adult↗
PubMed1993

Cardiovascular reflex testing and pupil cycle time in open-angle glaucoma.

The aim of the study is to assess the value of function tests of the autonomic nervous system in open-angle glaucoma by testing the cardiovascular reflexes and pupil cycle time. The experimental group consisted of 19 glaucoma subjects with controlled intraocular pressure. The control group consisted of 20 healthy volunteers. The Valsalva test has proven to be considerably accurate in the assertion of autonomic dysfunction (p < 0.05). Pupil cycle time was significantly prolonged (p < 0.001). These results confirm the role of autonomic dysfunction in open-angle glaucoma.

Autonomic Nervous System Diseases↗
PubMed2005

The assessment of baroreflex sensitivity in patients with chronic kidney disease: implications for vasomotor instability.

PURPOSE OF REVIEW: Autonomic dysfunction is well recognized in chronic kidney disease. The baroreflex arc is an important component of the autonomic nervous system and influences vasodilatation and heart rate in response to information derived from baroreceptors located in the aorta and common carotid arteries. Appropriate regulation of systemic blood pressure is therefore dependent upon the integrity and normal function of the baroreflex arc. Vasomotor instability during haemodialysis has traditionally been identified as a pathophysiological state largely due to the failure of compensatory mechanisms during ultrafiltration. This review article discusses autonomic dysfunction as a key factor contributing to the systemic haemodynamic instability that may occur during dialysis. RECENT FINDINGS: Relationships have begun to be established between markers of reduced baroreflex sensitivity and abnormal cardiovascular structure, such as left ventricular dysfunction, left ventricular hypertrophy and arterial stiffness. SUMMARY: Pathological relationships between cardiovascular structure and function remain important in the understanding of both haemodynamic instability and cardiovascular mortality in chronic kidney disease patients. Understanding the associations between conventional markers of haemodynamic instability and autonomic function will allow early identification of patients likely to benefit from individualizing dialysis therapy.

Arrhythmias, Cardiac↗
PubMed2005

Impaired vagal modulation of heart rate in individuals with Down syndrome.

The attenuated heart rate (HR) and blood pressure (BP) response to exercise in individuals with Down syndrome (DS) has been attributed to autonomic dysfunction, which has been associated with obesity. Our purpose was to determine the role of autonomic control of HR to the attenuated chronotropic response observed in individuals with DS. We evaluated spectral analysis of HR variability (HRV) in 13 individuals with (BMI 32+/-5 kg/m(2), P<0.05) and 14 without DS (BMI 26+/-3 kg/m(2)) by means of 2 min isometric handgrip at 30% of maximal force followed by recovery. Noninvasive measures of HR (ECG) and systolic BP (SBP) (Portapres) were recorded continuously. The increases in HR and SBP, and decrease in high frequency (HF) component were significantly greater in controls than in individuals with DS (P<0.05) during handgrip. The increase in LF/HF ratio was not significantly affected by handgrip and was comparable in both groups. During recovery, the decreases in HR, SBP, and LF/HF ratio, and the increase in HF were significantly greater in controls than in individuals with DS (P<0.05). Controlling for BMI did not alter these results. The attenuated HR and SBP response to the handgrip test in individuals with DS is explained by blunted vagal modulation. Our study suggests that autonomic dysfunction in individuals with DS might be independent of obesity.

Adolescent↗
PubMed1999

Overview of molecular mechanisms in chagasic cardioneuromyopathy and achalasia.

Evidence accumulated by our investigations over the years give adequate proof for the existence of circulating antibodies in Chagas disease which bind to beta adrenergic and muscarinic cholinergic receptor of myocardium. The interaction of agonist-like antibodies with neurotransmitter receptors, triggers in the cells intracellular signal transductions that alter the physiological behaviour of the target organs. These events convert the normal cells into pathologically active cells. The interaction of antibodies with heart beta adrenergic and cholinergic receptors triggers physiologic, morphologic, enzymatic and molecular alterations, leading to tissue damage. The analysis of the prevalence and distribution of these antibodies reveals a strong association with cardiac and esophageal autonomic dysfunction in seropositive patients in comparison with those without alteration of the heart and esophagus autonomic disorders: therefore, the presence of these antibodies may partially explain the cardiomyoneurophathy and achalasia of Chagas disease, in which the sympathetic and parasympathetic systems are affected. The deposit of autoantibodies behaving like an agonist on neurotransmitter receptors, induceds desensitization and/or down regulation of the receptors. This in turn, could lead to a progressive blockade of neurotransmitter receptors, with sympathetic and parasympathetic dennervation, a phenomenon that has been described during the course of Chagas cardioneuropathy and achalasia. The clinical relevance of these findings is the demonstration, using biomolecules, of a strong association between the existence of circulating autoantibodies against peptides corresponding to the second extracellular loop of the human heart beta, adrenoceptor and M2 cholinoceptor in chagasic patients, and the presence of dysautonomic symptoms, making these autoantibodies a proper early marker of heart and digestive autonomic dysfunction.

Antibodies, Protozoan↗
PubMed1996

Altered blood pressure profile, autonomic neuropathy and nephropathy in insulin-dependent diabetic patients.

To evaluate the relationship between autonomic neuropathy (AN) and nephropathy we measured 24-h blood pressure (BP) and overnight urinary albumin excretion (UAE) in 38 patients with insulin dependent diabetes mellitus (IDDM). Autonomic function was evaluated by the heart rate response to deep breathing. Valsalva maneuver, heart rate at rest and BP variation with posture. Sympathetic cutaneous reflex was also tested in both inferior and superior limbs. Patients with mean day diastolic BP (DDBP) < or = 90 mmHg without AN (N = 15) compared to 12 normal controls had similar BP values, but compared to those with DDBP < or = 90 mmHg and AN (N = 12) they had lower night diastolic BP (NDBP) (66 +/- 4.8 vs 72 +/- 8.8 mmHg: p < 0.05) and UAE (9.8 +/- 2.3 vs 107.2 +/- 3.5 micrograms/min; p < 0.001). No difference in DDBP was observed between these two diabetic groups (80 +/- 3.9 vs 83 +/- 6.1 mmHg). Of the 11 patients with DDBP > 90 mmHg, only three were free of AN and only two of the eight with AN where free of diabetic nephropathy. The percentage day/night changes in systolic BP were lower in patients with AN (13 vs 7.9%; p < 0.05) and were inversely related to autonomic score, used as an index of the degree of autonomic dysfunction (r = -0.48; p < 0.01) and to UAE (r = -0.39; p < 0.05). Furthermore, UAE correlated with autonomic score (r = 0.69; p < 0.0001) and with NDBP (r = 0.44; p < 0.01). Our results show that AN in IDDM patients is associated with a reduced nocturnal fall in BP and suggest a pathogenic role of autonomic dysfunction in the development of diabetic nephropathy, possibly favoring both BP elevation during the night and increases in intraglomerular pressure.

Adolescent↗
PubMed2001

Autonomic neuropathy is linked to nocturnal hypoxaemia and to concentric hypertrophy and remodelling in dialysis patients.

BACKGROUND: Autonomic dysfunction and sleep apnoea are frequent complications of chronic renal failure. Since nocturnal hypoxaemia in sleep apnoea dampens autonomic reflexes, we postulated that altered autonomic control is in part linked to nocturnal hypoxaemia in uraemic patients. METHODS: To test the hypothesis we performed continuous monitoring of O(2) saturation during night by pulse oximetry (Ohmeda-Biox) as well as echocardiography, 24-h ambulatory blood pressure monitoring, and standard tests of autonomic function in 50 patients on chronic dialysis (40 on haemodialysis and 10 on CAPD). For haemodialysis patients all studies were performed during a mid-week non-dialysis day. RESULTS: Twenty-five patients had at least one episode of nocturnal hypoxaemia (median 13, interquartile range 4-31) while the other 25 patients had no episodes at all. Minimal and average SaO(2) were strongly interrelated (r = 0.64, P = 0.0001). In a multiple regression model, besides age, average nocturnal SaO(2) was the only independent predictor of the parasympathetic function. Similarly, average nocturnal SaO(2) was the only independent predictor of the autonomic response to standing. Sex, 24-h mean arterial pressure, body mass index, haematocrit, serum albumin, serum parathyroid hormone and duration of dialysis treatment had no independent effect on the autonomic tests. Interestingly, the average nocturnal SaO(2) and the interaction between the responses to the autonomic tests were independently related to posterior-wall thickness. This interaction term represented also the stronger independent predictor of the relative wall thickness of the left ventricle. In a multiple logistic regression model the interaction parasympathetic-sympathetic function was the only independent predictor of concentric remodelling or hypertrophy, while average nocturnal SaO(2) entered into this model (P = 0.03) only after exclusion of the autonomic function interaction term. CONCLUSIONS: Thus, altered cardiovascular autonomic control appears to be linked to nocturnal hypoxaemia and to concentric hypertrophy or remodelling in dialysis patients. Since nocturnal hypoxaemia is an established cardiovascular risk factor, altered autonomic control is a potential mechanism whereby hypoxaemia may trigger cardiovascular events in dialysis patients. It remains to be seen whether the link between nocturnal hypoxaemia and autonomic dysfunction is a causal one.

Adult↗
PubMed1990

Neuroaxonal dystrophy in aging human sympathetic ganglia.

Autonomic dysfunction is an increasingly recognized problem in aging animals and man. The pathologic changes that produce autonomic dysfunction in human aging are largely unknown; however, in experimental animal models specific pathologic changes have been found in selected sympathetic ganglia. To address whether similar neuropathologic changes occur in aging humans, the authors have examined paravertebral and prevertebral sympathetic ganglia from a series of 56 adult autopsied nondiabetic patients. They found significant, specific, age-related neuropathologic lesions in the prevertebral sympathetic superior mesenteric ganglia of autopsied patients. Markedly swollen dystrophic preterminal axons compressed or displaced the perikarya of principal sympathetic neurons. Ultrastructurally, these swollen presynaptic axons contained abundant disoriented neurofilaments surrounded by peripherally marginated dense core vesicles. Immunohistochemical studies demonstrated that dystrophic axons contained tyrosine hydroxylase and neuropeptide tyrosine (NPY)-like immunoreactivity but not other neuropeptides (VIP, substance P, gastrin-releasing peptide [GRP]/bombesin, met-enkephalin). Similar to the animal models of aging, lesions were much more frequent in the prevertebral superior mesenteric ganglia than in the paravertebral superior cervical ganglia. These studies demonstrate anatomic, peptidergic, and pathologic specificity in the aging human nervous system similar in many respects to that which the authors have described in experimental animal models. Neuroaxonal dystrophy in the sympathetic nervous system may underlie poorly understood alterations in clinical autonomic nervous system function that develop with age.

Adult↗
PubMed1996

Twenty-four hour heart period variability in systemic sclerosis.

OBJECTIVE: In patients with systemic sclerosis (SSc), an autonomic dysfunction has been implicated in the pathogenesis of Raynaud's phenomenon and gastrointestinal symptoms. To evaluate cardiovascular autonomic function we analyzed the heart rate variability (HRV) on 24 h electrocardiogram recordings. METHODS: In 50 patients diagnosed with SSc and 24 control subjects HRV was analyzed for both frequency and time domain. RESULTS: Frequency domain analysis showed reduction of low frequency and high frequency values in the patients with SSc compared to controls (5.52 +/- 0.74 vs 6.04 +/- 0.78 In(ms2), p = 0.007; and 4.17 +/- 0.97 vs 4.74 +/- 0.97 In(ms2), p = 0.021, respectively). Analysis in time domain showed no significant differences in any variable between groups. There were no significant differences between the diffuse and the limited form of SSc. Number of ventricular ectopic beats, prevalence of frequent ventricular ectopy, and supraventricular tachycardia episodes were increased in the patients with SSc compared to controls. CONCLUSION: Spectral analysis of heart period variability suggests cardiovascular autonomic dysfunction in patients with SSc. Better understanding of this complication could help delineate new strategies for the treatment of SSc.

Adult↗
PubMed1992

Cardiovascular reflexes in patients with malignant disease.

Although some authors have reported clinical features of autonomic dysfunction in patients with malignant disease only a few systematic studies have been carried out. We have investigated the autonomic function of 48 patients with carcinoma or lymphoma by testing their cardiovascular reflexes, and compared their results with those of 62 healthy volunteers. Our patients showed a smaller increase in heart rate and a greater fall in blood pressure on standing up, as well as a smaller rise in blood pressure in response to contralateral handgrip. The study group showed a higher percentage of established sympathetic lesion (54.2% vs 27.4%, p: 0.008) and of atypical pattern of global autonomic function impairment (50% vs 24.2%, p: 0.03) than the control group. Our data suggest that patients with malignant disease suffer from a definite autonomic dysfunction.

Aged↗